The novel κ-opioid receptor agonist TRK-820 has no affect on the development of antinociceptive tolerance to morphine in mice

Abstract

The effects of the novel κ-opioid receptor agonist 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[ N-methyl- trans-3-(3-furyl)acrylamido]morphinan hydrochloride (TRK-820) on the development of antinociceptive tolerance to morphine were investigated in mice and compared with those of trans-3,4-dichloro- N-(2-(1-pyrrolidinyl)-cyclohexyl) benzenacetamide methane sulfonate hydrochloride (U-50,488H), a well-defined exogenous κ-opioid receptor agonist. Morphine (1.25–20 mg/kg, s.c.) produced a dose-related antinociceptive effect in the 51°C warm-plate test. Daily treatment with morphine (10 mg/kg, s.c.) resulted in the development of antinociceptive tolerance. The development of antinociceptive tolerance to morphine was dose-dependently suppressed by the co-administration of U-50,488H (1–10 mg/kg, s.c.) with morphine, but not TRK-820 (0.003–0.03 mg/kg, s.c.). These results suggest that TRK-820-sensitive κ-opioid receptor subtypes may not be involved in modulating the development of antinociceptive tolerance to morphine.